Combining lung-protective strategies in experimental acute lung injury: The impact of high-frequency partial liquid ventilation.

OBJECTIVE: To evaluate the independent and combined effects of high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on gas exchange, pulmonary histopathology, inflammation, and oxidative tissue damage in an animal model of acute lung injury. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Fifty New Zealand White rabbits. INTERVENTIONS: Juvenile rabbits injured by lipopolysaccharide infusion and saline lung lavage were assigned to conventional ventilation (CMV), PLV, HFOV, or high-frequency partial liquid ventilation (HF-PLV) with a full or half dose (HF-PLV1/2) of perfluorochemical (PFC). Uninjured ventilated animals served as controls. Arterial blood gases were obtained every 30 mins during the 4-hr study. Histopathologic evaluation was performed using a lung injury scoring system. Oxidative lung injury was assessed by measuring malondialdehyde and 4-hydroxynonenal in lung homogenates. MEASUREMENTS AND MAIN RESULTS: HFOV, PLV, or a combination of both methods (HF-PLV) resulted in significantly improved oxygenation, more favorable lung histopathology, reduced neutrophil infiltration, and attenuated oxidative damage compared with CMV. HF-PLV with a full PFC dose did not provide any additional benefit compared with HFOV alone. HF-PLV1/2 was associated with decreased pulmonary leukostasis compared with HF-PLV. CONCLUSIONS: The combination of HFOV and PLV (HF-PLV) does not provide any additional benefit compared with HFOV or PLV alone in a combined model of lung injury when lung recruitment and volume optimization can be achieved. The use of a lower PFC dose (HF-PLV1/2) is associated with decreased pulmonary leukostasis compared with HF-PLV and deserves further study.

[The impact of mechanical ventilation strategies that minimize atelectrauma in an experimental model of acute lung injury]. / O impacto de estratégias de ventilação mecânica que minimizam o atelectrauma em um modelo experimental de lesão pulmonar aguda.

OBJECTIVE: To evaluate whether ventilation strategies that target alveolar stabilization and prevention of atelectrauma would be associated with more favorable physiologic outcomes in a combined model of acute lung injury. METHODS: Thirty-nine rabbits were instrumented and ventilated with FiO(2) of 1.0. Combined lung injury was induced by an infusion of lipopolysaccharide and tracheal saline lavage. Animals were randomized to receive conventional ventilation with tidal volume of 10 ml/kg, PEEP of 4 cm H(2)O; conventional ventilation with surfactant (Infasurf, 3 mg/kg IT); partial liquid ventilation (18 ml/kg of perflubron IT); or high-frequency oscillatory ventilation with mean airway pressure of 14 cm H(2)O and frequency of 4 Hz. Uninjured ventilated animals served as controls. Conventional ventilation with surfactant, partial liquid ventilation and control groups were ventilated with settings identical to the conventional ventilation group. Animals were studied for 4 hours, during which serial blood gas measurements were obtained. After sacrifice, lungs were harvested for injury grading by a microscopic lung injury score and measurement of 4-hydroxy-nonenal, a marker of lipid peroxidation. RESULTS: Conventional ventilation resulted in hypoxia and greater evidence of lung injury. Animals treated with partial liquid ventilation, high-frequency oscillatory ventilation or conventional ventilation with surfactant had adequate oxygenation, but conventional ventilation with surfactant resulted in higher lung injury scores and increased pulmonary oxidative damage. CONCLUSION: Strategies that minimize atelectrauma (partial liquid ventilation and high-frequency oscillatory ventilation) are associated with adequate oxygenation and attenuated lung injury. Surfactant improves oxygenation in comparison to conventional ventilation alone but resulted in increased injury, presumably because the inadequately low PEEP was insufficient to stabilize the alveoli during expiration.

O impacto de estratégias de ventilação mecânica que minimizam o atelectrauma em um modelo experimental de lesão pulmonar aguda / The impact of mechanical ventilation strategies that minimize atelectrauma in an experimental model of acute lung injury

OBJETIVO: Avaliar se estratégias ventilatórias que buscam a estabilização alveolar e a prevenção do atelectrauma estão associadas a desfechos fisiológicos mais favoráveis em um modelo experimental de lesão pulmonar aguda combinada. MÉTODOS: Trinta e nove coelhos foram instrumentados e ventilados com uma fração inspirada de oxigênio (FiO2) de 1,0. A lesão pulmonar foi induzida pela infusão venosa de lipopolissacarídeo de E. coli e por repetidas lavagens traqueais com solução salina. Os animais foram randomizados a receber ventilação mecânica convencional com volume corrente de 10 ml/kg, pressão expiratória final (PEEP) de 4 cm H2O; ventilação mecânica convencional com surfactante (Infasurf, 3 mg/kg, ET); ventilação líquida parcial (18 ml/kg de perflubron, ET); ou ventilação oscilatória de alta freqüência, com pressão média de via aérea de 14 cm H2O e freqüência de 10 Hz. Animais sadios submetidos a instrumentação e ventilação convencional serviram como controles. Os grupos ventilação mecânica convencional com surfactante, ventilação líquida parcial e controle foram ventilados com parâmetros idênticos ao grupo ventilação mecânica convencional. Os animais foram estudados por 4 horas, durante as quais gasometrias arteriais foram obtidas a cada 30 minutos. Após o sacrifício, os pulmões foram retirados para graduação de lesão através de um escore de dano histológico e dosagem de 4-hidroxi-nonenal, um marcador de peroxidação lipídica. RESULTADOS: A ventilação mecânica convencional resultou em hipoxemia e lesão pulmonar significativa. Animais tratados com ventilação líquida parcial, ventilação oscilatória de alta freqüência ou ventilação mecânica convencional com surfactante apresentaram oxigenação adequada, mas a ventilação mecânica convencional com surfactante resultou em escores de lesão pulmonar mais elevados e maior dano oxidativo. CONCLUSÕES: Estratégias que minimizam o atelectrauma (ventilação mecânica convencional e ventilação oscilatória de alta freqüência) estão associadas a oxigenação adequada e atenuação da lesão pulmonar. A reposição de surfactante melhora a oxigenação em comparação com a ventilação mecânica convencional, mas resulta em lesão pulmonar aumentada, presumivelmente porque o PEEP inadequadamente baixo foi insuficiente para estabilizar os alvéolos durante a expiração.